Beta-Oxidation of Fatty Acid Definition
- Acetyl-CoA is produced by the catabolic process known as Beta-oxidation of fatty acid, which breaks down fatty acid molecules in the cytoplasm of prokaryotes and the mitochondria of eukaryotes.
- When acetyl-CoA reaches the citric acid cycle, coenzymes NADH and FADH2 are used in the electron transport chain.
- Because the fatty acid’s beta carbon is oxidised to a carbonyl group, the process is known as “beta oxidation.”
Location of Beta-Oxidation of Fatty Acid8
In eukaryotes, beta-oxidation takes place in the mitochondria, while in prokaryotes it takes place in the cytoplasm.
Substances: H2O and free fatty acids.
Products One acetyl CoA, one NADH, as well as one FADH2 are generated whenever a two-carbon group is withdrawn from a fatty acid chain.
The Pathway of Beta-Oxidation
- In the mitochondria, the fatty acid performs a sequence of oxidation and hydration reactions that remove a two-carbon group from the fatty acid chain (in the form of acetyl CoA) and produce one NADH and one FADH2. They join the electron transport chain in order to generate five ATP.
- Another 12 ATP will be produced when the acetyl CoA generated enters the citric acid cycle and, subsequently, the electron transport chain. The cycle repeats, removing another two-carbon group with each cycle turn, till acetyl CoA or propionyl CoA are produced from the long-chain fatty acid.
- Through three enzymatic reactions that need cofactors of biotin and vitamin B12, propionyl CoA may be transformed into succinyl CoA. Succinyl CoA can subsequently join the citric acid cycle.
- Activation of fatty acids
- Long-chain fatty acids are activated in the cytoplasm of the cell by ATP and coenzyme A, resulting in the formation of fatty acyl-CoA. Mitochondria activate short-chain fatty acids.
- Pyrophosphatase cleaves pyrophosphate (PPi) into two inorganic phosphates when the ATP is converted to AMP and pyrophosphate (AMP) (2 Pi). Fatty acid activation uses the equivalent of two ATP molecules, since two high-energy phosphate bonds are broken.
- Transport of fatty acyl-CoA from the cytosol into mitochondria
- In the outer mitochondrial membrane, carnitine and fatty acyl-CoA from the cytosol combine to produce fatty acylcarnitine. Carnitine acyltransferase I (CAT I), also called carnitine palmitoyltransferase I, is an enzyme (CPT I). When fatty acylcarnitine reaches the inner membrane, it transforms back into fatty acyl-CoA and moves into the matrix. It is followed by carnitine acyltransferase II (CAT II).
- Malonyl-CoA, a by-product of the production of fatty acids, inhibits the enzyme carnitine acyltransferase I, which catalyses the transfer of acyl groups from coenzyme A to carnitine. Malonyl-CoA hence limits the transfer of fatty acids into mitochondria during their cytosolic production, preventing an unnecessary cycle (synthesis followed by immediate degradation).
- The beta-oxidation of the fatty acid acyl-CoA takes place within the mitochondrion.
- β-Oxidation of even-chain fatty acids
The first three stages of the -oxidation spiral, which resemble the TCA cycle between succinate and oxaloacetate in that all reactions require the carbon of a fatty acyl-CoA, The process is repeated once all of the even-chain fatty acyl-carbon CoAs have been transformed into acetyl-CoA.
- In the first stage, a fatty acyl-CoA provides hydrogen to FAD. Enoyl-CoA is created when a double bond forms between the – and -carbons. The
- By interacting with the electron transport chain, the resultant FADH2 creates ATP.
- Acyl-CoA dehydrogenase, an enzyme (Multiple variants of this enzyme)
- A-hydroxyacyl-CoA is created when H2O is added across the double bond.
- Enoyl-CoA hydratase, an enzyme
- NAD+ converts hydroxyacyl-CoA into ketoacyl-CoA. ATP is produced when freshly generated NADH comes into contact with the electron transport chain.
- L-3-hydroxyacyl-CoA dehydrogenase is an enzyme that only reacts with the L-isomer of hydroxyacyl-CoA.
- A thiolase that needs coenzyme A breaks the connection between the alpha and beta carbons of the ketoacyl-CoA. The two carbons at the carboxyl end of the original fatty acyl-CoA are converted to acetyl-CoA, and a fatty acyl-CoA that is two carbons smaller than the original is made using the remaining carbons.
- Enzyme: β -ketothiolase
- These four stages are repeated by the shorter fatty acyl-CoA. Repetition occurs until all of the original fatty acyl-carbon CoA’s are changed into acetyl-CoA.
Energy Yield for Even-chain Fatty Acids
- The by-products of oxidation are used to produce energy.
- Seven times are performed on the palmitoyl-CoA, which has 16 carbons.
- A 4-carbon fatty acyl-CoA (butyryl-CoA) is split into two acetyl-CoAs in the last repeat.
- Eight acetyl-CoA, seven FADH2, seven NADH, and one palmitoyl-CoA are produced when one palmitoyl-CoA is oxidised.
- For a combined output of roughly 10.5 ATP, the seven FADH2 individually produce about 1.5 ATP.
- Each of the seven NADH produces roughly 2.5 ATP, for a total of 17.5 ATP.
- The eight acetyl-CoA may join the TCA cycle, yielding a combined total of roughly 80 ATP (about 10 ATP per acetyl-CoA).
- About 108 ATP are generated when palmitoyl-CoA is converted to CO2 and H2O.
- Due to the fact that palmitate must first be activated (which needs the equivalent of 2 ATP) before it can be oxidised (108 ATP 2 ATP = 106 ATP), palmitate reaches the cell from the blood and produces roughly 106 net units of ATP.
- Different quantities of ATP will be produced by the oxidation of various fatty acids.
Oxidation of odd-chain and unsaturated fatty acids
Odd-chain fatty acids. Acetyl-CoA and propionyl-CoA are produced by odd-chain fatty acids.
- The four stages of the oxidation spiral are repeated by these fatty acids, creating acetyl-CoA up to the last cleavage. At this moment, propionyl-CoA is formed from the three remaining carbons.
- Acetyl-CoA cannot be converted to glucose, only protonated-CoA can.
Unsaturated fatty acids: Which account for approximately half of the fatty acid remains in human lipids, need additional enzymes in relation to the four enzymes that catalyse the repeated phases of the oxidation spiral.
- Depending on whether the double bond is attached to an even or an odd number of carbons, the reaction pathway changes.
- Until an unsaturated fatty acid double bond reaches close to the carboxyl end of the fatty acyl chain, oxidation takes place.
(1) An isomerase will change the final cis-3 to a trans-2 fatty acid if the double bond began at an odd carbon number (such as 3, 5, 7, etc.).
(2) If the double bond was formed at an even carbon number (such as 4, 6, 8, etc.), the resulting trans-2, cis-4 fatty acid will be reduced by a 2,4-dienoyl-CoA reductase, which produces a trans-3-acyl-CoA and NADP1 and needs NADPH as an input. To enable further oxidation, the isomerase will change the trans-3 fatty acyl-CoA to a trans-2 fatty acyl-CoA.
ATP yield for unsaturated fatty acids
(1) If the double bond starts at an odd carbon position, there will be 1.5 ATP fewer for each unsaturation at the odd carbon position compared to a completely saturated fatty acid of the same carbon length because one less FADH2 is created for each unsaturation.
(2) Due to the utilisation of NADPH in the phase catalysed by the 2,4-dienoyl-CoA reductase, there is one less NADH equivalent (or 2.5 ATP) generated if the double bond originated at an even-numbered carbon position than there would be for an equal length of fully saturated fatty acid.
Overall Reaction of Beta oxidation
One beta oxidation cycle results in the following overall reaction:
Cn-acyl CoA + FAD + NAD+ + H2O + CoA → Cn-2-acyl CoA + FADH2 + NADH + H+ + acetyl CoA
Acyl CoA dehydrogenas: The enzyme acyl CoA dehydrogenase creates a double bond between the carbon atoms of the fatty acid chain at positions and. It creates a single FADH2.
Enoyl CoA hydratase: Breaks the double bond between the and carbon atoms in the fatty acid chain by incorporating a water molecule into the chain.
3-Hydroxy-acyl CoA dehydrogenase: Dehydrogenates the fatty acid chain once again, creating a double bond between the oxygen molecule and the carbon atom. 3-Hydroxy-acyl CoA dehydrogenase. It creates a single NADPH.
Acyl CoA acyltransferase: Adds CoA to the carbon atom after cleaving acetyl CoA from the end of the fatty acid chain.
Regulation of Beta-oxidation of Fatty Acids
The mechanisms that govern oxidative phosphorylation also regulate oxidation (i.e., by the demand for ATP).
Activators: Epinephrine increases oxidation by triggering a cAMP-dependent protein kinase, which phosphorylates HSL and then activates it. Fatty acids and glycerol are released from adipose tissue when HSL is activated, allowing for -oxidation.
Inhibitors: By dephosphorylating HSL, insulin prevents oxidation. This prevents the release of fatty acids from adipose tissue.
The primary mechanism for oxidising fatty acids, the body’s principal energy source, is -oxidation.
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